Characterization of alternative sPD-1 isoforms reveals that ECD sPD-1 signature predicts an efficient antitumor response.

ABSTRACT: Soluble PD-1 is a dissociated form of membrane PD-1 broadly present in cancer, infections, or autoimmune diseases. However, the clinical significance of sPD-1 remains controversial due to the uncertainty of its isoforms, origin, and production mechanism. Here, using antibodies specifically binding to the intracellular domain of PD-1, we identified two sPD-1 isoforms in cancers at the protein level: FL sPD-1 containing both the extra- and intracellular domains of PD-1, and ECD sPD-1 containing only the extracellular fragment. Subsequently, we tracked their origin and found that in tumor models, both sPD-1 isoforms were generated by activated CD8 T cells highly expressing membrane PD-1. However, ECD sPD-1 was released from live PD-1⁺T cells by matrix metalloproteinases, while FL s

SUBMITTER: Hou P 

PROVIDER: S-EPMC11897324 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature